Long-acting mucoadhesive thermogels for improving topical treatments of dry eye disease.

Abstract

Dry eye disease (DED) is the most common ocular disorder that causes persistent discomfort and blurry vision in patients. Despite pharmacotherapy strategies, the current topical administration of eye drops remains a great challenge owing to their low bioavailability and short residence time. Herein, we demonstrate an effective topical treatment of DED via rational design of a long-acting and mucoadhesive drug delivery system. Specifically, the drug carrier is a chemically ternary material system consisting of gelatin that serves as an enzyme-mediated degradable matrix, poly(N-isopropylacrylamide) as a thermo-responsive regulator, and lectin Helix pomatia agglutinin as a mucus-binding component. The long-acting drug release performance is exploited via initiator effects during the synthesis of the thermo-responsive polymer, while the mucoadhesive feature is inherited from the mucus-binding material. In a rabbit model of DED, a pharmacotherapy based on one-time topical administration of epigallocatechin gallate-loaded carrier onto the cul-de-sac could effectively repair the defective corneal epithelium via mitigating cellular inflammation, oxidative stress, and cell apoptosis for a sustained period over 14days. These findings on the initiator and synergy effects in the development of the advanced ophthalmic formulation show great promise for efficient management of complex ocular diseases by a simple topical administration route.